Method for producing an aperture plate

ABSTRACT

An aperture plate is manufactured by plating metal around a mask of resist columns having a desired size, pitch, and profile, which yields a wafer about 60 μm thickness. This is approximately the full desired target aperture plate thickness. The plating is continued so that the metal overlies the top surfaces of the columns until the desired apertures are achieved. This needs only one masking/plating cycle to achieve the desired plate thickness. Also, the plate has passageways formed beneath the apertures, formed as an integral part of the method, by mask material removal. These are suitable for entrainment of aerosolized droplets exiting the apertures.

RELATED APPLICATIONS

This application claims priority U.S. Provisional Application No.62/002,435, filed May 23, 2014, the entire disclosure of which isincorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The invention relates to manufacture of aperture plates (or “vibratingmembranes”) for aerosol (or “nebulizer”) devices.

Prior Art Discussion

An aperture plate is used for aerosol delivery of liquid formulations ina controlled liquid droplet size suitable for pulmonary drug delivery.The ideal nebulizer is one which assures a consistent and accurateparticle size in combination with an output rate that can be varied todeliver the drug to the targeted area as efficiently as possible.Delivery of the aerosol to the deep lung such as the bronchi andbronchiole regions requires a small and repeatable particle sizetypically in the range of 2-4 μm in general, outputs greater than 1ml/min are required.

U.S. Pat. Nos. 6,235,177, 7,066,398 and 8,398,001 describe an approachto manufacturing an aperture plate in which a wafer is built onto amandrel by a process of electro-deposition where the dissolved metalcations in the plating bath (typically Palladium and Nickel) are reducedusing electrical current from the liquid form to the solid form on thewafer. Material is reduced only to the conducting surface on the mandreland not to photo resist islands which are non-conducting. The aperturehole size and profile are defined by the three dimensional growth ofplated materials, thus, electroforming. After the conclusion of theplating process, the mandrel/wafer assembly is removed from the bath andthe wafer peeled from the mandrel for subsequent processing into anaperture plate.

However, a problem with this approach is that the wafer thickness isintertwined with the placement density of the non-conducting resistislands, i.e. the thicker the wafer, the further the distance betweenthe non-conduction resist islands, and the smaller the aperture density.As a result, it is not possible to increase the aperture density toabout 90,000 holes per square inch (approx. 650 mm²). Reduced waferthickness is Used to alleviate this issue. If a wafer has a thickness inthe range of 50 to 54 μm non-standard drives are required. Also, areduction in the aperture plate thickness alters the harmonics andnatural frequency of the core assembly. To drive this optimally togenerate an acceptable flow rate output, it is necessary to alter thedrive frequency. This is disadvantageous as it requires the development,manufacture, and supply of a matching drive controller which hasconsequential cost and lead time implications.

Photo-defined technology as described in WO2012/092163A andWO2013/186031A allows a large number of holes to be produced per unitarea because it applies standard wafer processing technology to definethe aperture plate hole size and profile through photolithography, thus,“photo-defined”.

This technology may involve plating multiple layers to achieve desiredaperture plate geometry and profile, for example, a first layer normallycalled the outlet or droplet size defining layer, and subsequentlyimparting a second layer on top of this which is normally called theinlet or reservoir layer. It can be challenging to achieve the correctlevels of interfacial adhesion between both layers. And the process ismore complex than that for electroforming.

US2006/0203036 describes an approach to fabricating an orifice plate inwhich there is plating on rings, so that plated material within therings forms apertures which narrow to a minimum at about half theirdepth.

The invention is directed towards providing an improved method toaddress the above problems.

SUMMARY OF THE INVENTION

According to the invention, there is provided a method of manufacturingan aperture plate wafer, the method comprising providing a substrate ofconductive material, applying a mask over the substrate in a pattern ofcolumns having top surfaces, electroplating (3) around the columns,removing the mask to provide a wafer of the electroplated material withaerosol-forming holes,

-   -   characterized in that,    -   the electroplating step partially over-plates the top surfaces        of the columns while leaving aerosol-forming apertures of a        desired size,    -   the columns have a height in the range of 40 μm to 70 μm.

In one embodiment, the columns have a height in the range of 55 μm to 65μm.

In one embodiment, the column width dimension is in the range of 20 μmto 40 μm.

In one embodiment, the column width dimension is in the range of 25 μmto 35 μm.

In one embodiment, the combined aperture plate wafer thickness achievedby the column height and the height of over-plating is in the range of50 μm to 70 μm.

In one embodiment, the aperture size is in the range of 2 μm to 6 μm.

In one embodiment, the over-plating is controlled and the columndimensions are chosen to also achieve a desired slope of wafer materialtowards the aerosol-forming apertures to achieve a funnelling effect forliquid in use.

In one embodiment, the wafer is formed into a dome shape which isconcave on the side of the apertures, and the extent of curvature andthe shape of the over-plated metal is chosen to provide a funnellingeffect for liquid towards the apertures.

In one embodiment, the top surfaces of at least some columns aregenerally convex.

In one embodiment, the columns are configured so that when the maskingmaterial is removed they form passageways aligned with the apertures andbeing shaped for entrainment of droplets form the apertures.

In one embodiment, at least some of the columns have a configurationwidening towards the substrate so that after removal of the maskingmaterial they form passageways which widen in a direction away from theapertures.

In one embodiment, the passageways are gradually tapered with aconsistent slope.

Preferably, the passageways have a length in the range of range of 40 μmto 70 μm.

In another aspect, the invention provides an aperture plate comprising abody of metal configured with aerosol-forming apertures in a top surfaceand passageways aligned with and beneath the apertures, wherein themetal forms convex shapes around the apertures to provide afunnel-shaped entrance to the apertures.

Preferably, said passageways have a length in the range of 40 μm to 70μm. In one embodiment, the passageways widen towards the lower side ofthe plate.

In one embodiment, the passageways have a length of 55 μm to 65 μm andthe aperture plate has a thickness in the range of 50 μm to 70 μm; andwherein the passageways have a width in the range of 20 μm to 40 μm. Inone embodiment, the passageways have a width in the range of 25 μm to 35μm.

In another aspect, the invention provides an aerosol-forming devicecomprising an aperture plate as defined above in any embodiment, asupport for the aperture plate, and a drive for the aperture plate.

According to the invention, there is provided a method of manufacturingan aperture plate wafer, the method comprising providing a substrate ofconductive material, applying a mask over the substrate in a pattern ofcolumns, electroplating the spaces around the columns, removing the maskto provide a wafer of the electroplated material with aerosol-formingholes where the mask columns were, wherein the electroplating steppartially over-plates the tops of the columns while leavingaerosol-forming apertures of a desired size.

In One embodiment, the column height is chosen to achieve a desiredwafer thickness.

In one embodiment, the columns have a height in the range of 40 μm to 70μm, and preferably 55 μm to 65 μm. In one embodiment, the column widthdimension is in the range of 20 μm to 40 μm, preferably 25 μm to 35 μm.

In one embodiment, the combined wafer plate achieved by the columnheight and the height of over-plating is in the range of 50 μm to 70 μm.Preferably, the aperture size is in the range of 2 μm to 6 μm.

In one embodiment, the over-plating is controlled and the columndimensions are chosen to also achieve a desired slope of wafer materialtowards the aerosol-forming apertures to achieve a funnelling effect forliquid. In one embodiment, the wafer is formed into a dome shape whichis concave on the side of the apertures, and the extent of curvature andthe shape of the over-plated metal is chosen to provide a funnellingeffect for liquid towards the apertures.

In one embodiment, at least some columns have a generally convex topsurface.

In one embodiment, the columns are configured so that when the maskingmaterial is removed they form passageways aligned with the apertures andbeing shaped for entrainment of droplets form the apertures.

In one embodiment, at least some of the columns have a configurationwidening towards the substrate so that after removal of the maskingmaterial they form passageways which widen in a direction away from theapertures. Preferably, the passageways are gradually tapered with aconsistent slope. In one embodiment, the plated metal includes Ni. Inone embodiment, the plated metal includes Pd. In one embodiment, both Niand Pd are present in the plated metal.

In one embodiment, both Ni and Pd are present in the plated metal; andwherein the proportion of Pd is in the range of 85% w/w and 93% w/w, andpreferably about 89%, substantially the balance being Ni.

In one embodiment, the method comprises the further steps of furtherprocessing the wafer to provide an aperture plate ready to fit into anaerosol-terming device. In one embodiment, the wafer is punched andformed into a non-planar shaped aperture plate. In one embodiment, thewafer is annealed before punching.

In another aspect, the invention provides an aperture plate wafercomprising a body of metal whenever formed in a method as defined abovein any embodiment.

In another aspect, the invention provides an aperture plate comprising abody of metal configured with aerosol-forming apertures in a top surfaceand passageways aligned with and beneath the apertures.

In one embodiment, the metal body forms convex shapes around theapertures to provide a funnel-shaped entrance to the apertures. In oneembodiment, the passageways widen towards the lower side of the plate.

In one embodiment, the passageways are gradually tapered with a uniformsloped taper.

In one embodiment, the passageways have a length of 40 μm to 70 μm, andpreferably 55 μm to 65 μm, and the aperture plate has a thickness in therange of 50 μm to 70 μm.

In one embodiment, the passageways have a width in the range of 20 μm to40 μm, preferably 25 μm to 35 μm.

An aerosol-forming device comprising an aperture plate as defined abovein any embodiment.

DETAILED DESCRIPTION OF THE INVENTION Brief Description of the Drawings

The invention will be more clearly understood from the followingdescription of some embodiments thereof, given by way of example onlywith reference to the accompanying drawings in which:

FIGS. 1 to 4 are a series of cross-sectional views showing stages ofmanufacturing an aperture plate;

FIG. 5 is a cross-sectional view of a stage in an alternativeembodiment;

FIG. 6 is a cross-sectional diagram illustrating an alternative approachin which there are tapered openings below the aerosol-forming apertures;and

FIG. 7 shows an aperture plate of the type n FIG. 6 after it has beenformed into a dome shape.

DESCRIPTION OF THE EMBODIMENTS

Referring to FIGS. 1 to 4, the following are the main steps tomanufacture an aperture plate in one embodiment.

An aperture plate is manufactured by plating metal around a mask ofresist columns 2 having a height of about 45 μm, a diameter of about 30μm and a separation of about 30 μm. The plating is continued so that themetal 3 overlies the top surfaces of the columns until the desiredapertures 4 are achieved. This provides the benefits of bothphoto-defined technology (by reducing the aspect ratio near the apertureregion during electroforming) and aperture density by enabling moreclosely patterned resist islands, with need for only one masking/platingcycle to achieve the desired plate thickness.

In more detail, non-conductive photo-resist 2 is laid on to a mandrel 1substrate. This is developed to leave the upstanding columns 2 whereholes are required. The tops of the columns 2 are approximately convex.The mandrel is placed in an electroforming tank. As the platingcontinues, the space between the columns 2 of developed photo resist isin-filled with the plating material. This is typically a PdNi alloymatrix, or it could alternatively be Nickel or a Nickel Cobalt alloymatrix.

The plating is initially to the extent shown in FIG. 2 and is continuedso that over-plating occurs as shown in FIG. 3. This plating is stoppedjust in time to create 2 to 6 μm holes 4 as shown also in FIG. 3.

The diametrical size accuracy of these holes can be improved by slowingdown the plating deposition activity as the holes are being formed. Thisprevents ‘overshoot’ resulting in smaller or occluded holes with thepossibility of a thicker than desired wafer construction. The 45 μmcolumn height is so chosen such that when the plating is stopped (FIG.3) the holes are typically 2 to 6 μm and preferably 2 to 5 μm, which isrequired to produce droplets in the inhalable range for nebulisation,and concurrently the wafer thickness is in the range of 60 to 62 μm inone embodiment.

The convex shape of the entry surfaces to the apertures in addition tothe concave shape of the overall domed shaped aperture plate (FIG. 7)provides effective funnelling of the liquid towards the aerosol-formingapertures 4, thereby minimising the residual volume of the drug in thenebuliser. When the photo-resist 2 is removed using an appropriatedissolving solvent, the full wafer cross-section is evident as depictedin FIG. 4. The cross-sectional profile under the hole 4 formspassageways directly under and aligned with the apertures. Because theyare formed by removal of the column resist they have the same length asthe heights of the columns 2. In use, these passageways under theapertures encourage entrainment of the aerosol towards the outlet of thenebuliser, thereby reducing coalescence with the resultant undesirableeffect of larger droplets being formed.

In an alternative embodiment (FIG. 5), photo-resist columns 11 have flattop surfaces over which the metal (12) is plated.

As evident from FIG. 6, in a plate 20 the remaining metal may formoutlet hole or passageway 24 sides that are tapered towards the aerosoloutlet direction. This drawing shows the wafer metal 21 formingaerosol-forming apertures 22. The liquid 23 is aerosolized through theapertures 22 to exit as droplets through the entrainment openings orpassageways 24 aligned with and below the apertures 22. Clearly, choiceof geometry of the resist columns decides the geometry of thepassageways.

FIG. 7 shows an aperture plate 30 with metal 31 forming apertures 32 anddroplet entrainment openings 34, after being formed into a dome shape.As noted above, this dome shape together with the convex shape of themetal between the apertures 32 helps to effectively funnel the liquid 33towards the apertures 32 in order to form droplets, which exit via theentrainment openings 34.

These much larger holes 34 in comparison (to the aperture diameter) canentrain the aerosol, almost into a laminar flow pattern. This reducesturbulence and consequential coalescence which can lead to anundesirable increase in droplet size. These openings may be tapered(FIGS. 6 and 7) or not (FIGS. 1-4).

The resultant wafer 10 has a greater number of holes, greater than44,100 per 650 mm² (square inch, Mesh 210), than the prior art and yetmaintains the same aperture plate thickness (approximately 61 μm) asmany commercially available products. This ensures that the existingdrive controllers (128 kHz) already in situ in many hospitals can beused for the aperture plate, alleviating the cost and considerable timerequired to be expended to develop a bespoke drive controller to ensurethat the correct frequency is available to achieve optimum aerosoloutput. It is also more conducive for meeting and exceeding the fatiguelife requirements. As there is single-layer plating it incorporates afine equiaxed microstructure.

It will be appreciated that the method provides the benefits of bothphoto-defined technology, partially decoupling the dependence of waferthickness to resist island patterning distance and increased aperturedensity, with the process simplicity of electroforming, because it needsonly one masking/plating cycle to achieve the desired plate thickness.

Those skilled in the electro-deposition field will appreciate how theplating conditions may be chosen to suit the circumstances, and theentire contents of the following documents are herein incorporated byreference: U.S. Pat. Nos. 4,628,165, 6,235,117, US2007023547,US2001013554, WO2009/042187, and Lu S. Y., Li J. F., Zhou Y. H., “Grainrefinement in the solidification of undercooled Ni—Pd alloys”, Journalof Crystal Growth 309 (2007) 103-111, Sep. 14, 2007. Generally, mostelectroplating solutions involving Palladium and Nickel would work orNickel only or indeed Phosphorous & Nickel (14:86) or Platinum. It ispossible that a non-Palladium wafer could be plated at the surface (1-3microns thick) in PdNi to impart more corrosion resistance. This wouldalso reduce the hole sizes if smaller openings were desired.

The resist geometry, such as height, width, and shape, is configured insuch a way as to increase the number of holes while maintaining thedesired wafer thickness. Further increase of hole density is alsopossible. For example, the invention in one embodiment achieves anaperture plate of about 4 times the density (moving from 210 to 420holes per 25 mm (linear inch) or from 44,100 to 176,400 holes per 650mm² (square inch), while still maintaining the typical 60 to 62 μmthickness range.

Adjusting the dimensions in FIG. 1, by reducing the column 2 diameter(30 μm) and dimensions between the columns 2 to say 15 μm has thepotential to increase the number of holes to 700 to 850 per 25 mm(linear inch).

The invention avoids need for two-layer photo defined technology toincrease the number of holes while maintaining the same wafer thickness.It also solves the problem of using standard plating defined technologyas referred to in the Prior Art Discussion with a greater number ofholes which will result in a lower thickness wafer, thus requiringsignificant changes to the core construction, or more typically thedrive controller, to find the optimum drive frequency.

The invention finds particular application where faster nebulisationtreatment times are required. This is usually required for hand-helddevices when aerosol is administrated through the mouth or nasalpassages in fully mobile patients. These are typically patients whoadminister nebulised drugs in a non-hospital setting.

This is in contrast to intubated hospital patients who are typically onmechanical ventilation where treatment times are less important as longas the patient gets the full prescribed dose.

Techniques for vibrating the aperture plates are described generally inU.S. Pat. Nos. 5,164,740; 5,586,550; and 5,758,637, which areincorporated herein by reference. The aperture plates are constructed topermit the production of relatively small liquid droplets at arelatively fast rate. For example, the aperture plates of the inventionmay be employed to produce liquid droplets having a size in the rangefrom about 2 μm to about 10 μm, and more typically between about 2 μm toabout 5 μm. In some cases, the aperture plates may be employed toproduce a spray that is useful in pulmonary drug delivery procedures. Assuch, the sprays produced by the aperture plates may have a respirablefraction that is greater than about 70%, preferably more than about 80%,and most preferably more than about 90% as described in U.S. Pat. No.5,758,637.

In some embodiments, such fine liquid droplets may be produced at a ratein the range from about 2 μl (microliters) per second to about 25 μl persecond per 1000 apertures. In this way, aperture plates may beconstructed to have multiple apertures that are sufficient to produceaerosolized volumes that are in the range from about 2 μl to about 25μl, within a time that is less than about one second. Such a rate ofproduction is particularly useful for pulmonary drug deliveryapplications where a desired dosage is aerosolized at a rate sufficientto permit the aerosolised medicament to be directly inhaled. In thisway, a capture chamber is not needed to capture the liquid dropletsuntil the specified dosage has been produced. In this manner, theaperture plates may be included within aerosolisers, nebulizers, orinhalers that do not utilise elaborate capture chambers.

The aperture plate may be employed to deliver a wide variety of drugs tothe respiratory system. For example, the aperture plate may be utilizedto deliver drugs having potent therapeutic agents, such as hormones,peptides, and other drugs requiring precise dosing including drugs forlocal treatment of the respiratory system. Examples of liquid drugs thatmay be aerosolized include drugs in solution form, e.g., aqueoussolutions, ethanol solutions, aqueous/ethanol mixture solutions, and thelike, in colloidal suspension form, and the like. The invention may alsofind use in aerosolizing a variety of other types of liquids, such asinsulin.

It will be appreciated that the invention allows the production of awafer from which nebuliser aperture plates are punched in one singleplating step and facilitates the creation of a larger number of holesthan that known today (typically up to 400%). Also, it facilitates theuse of aperture plates which are 60 to 62 μm thick. Also, it allows anincrease in the number of holes per unit of area while still being ableto control the plating thickness to a predetermined dimension.

The above in combination allows the creation of a higher outputnebuliser while still maintaining the standard drive controller and coreconstruction all of which is accomplished in a very economical manner.

1. A method of manufacturing an aperture plate wafer, the methodcomprising providing a substrate of conductive material, applying a maskover the substrate in a pattern of columns having top surfaces,electroplating around the columns, removing the mask to provide a waferof the electroplated material with aerosol-forming holes, wherein, theelectroplating step partially over-plates the top surfaces of thecolumns while leaving aerosol-forming apertures of a desired size, thecolumns have a height in the range of 40 μm to 70 μm.
 2. The method asclaimed in claim 1, wherein the columns have a height in the range of 55μm to 65 μm.
 3. The method as claimed in claim 1, wherein the columnwidth dimension is in the range of 20 μm to 40 μm.
 4. The method asclaimed in claim 1, wherein the column width dimension is in the rangeof 25 μm to 35 μm.
 5. The method as claimed in claim 1, wherein thecombined aperture plate wafer thickness achieved by the column heightand the height of over-plating is in the range of 50 μm to 70 μm.
 6. Themethod as claimed in claim 1, wherein the aperture size is in the rangeof 2 μm to 6 μm.
 7. The method as claimed in claim 1, wherein theover-plating is controlled and the column dimensions are chosen to alsoachieve a desired slope of wafer material towards the aerosol-formingapertures to achieve a funnelling effect for liquid in use.
 8. Themethod as claimed in claim 1, wherein the over-plating is controlled andthe column dimensions are chosen to also achieve a desired slope ofwafer material towards the aerosol-forming apertures to achieve afunnelling effect for liquid in use; and wherein the wafer is formedinto a dome shape which is concave on the side of the apertures, and theextent of curvature and the shape of the over-plated metal is chosen toprovide a funnelling effect for liquid towards the apertures.
 9. Themethod as claimed in claim 1, wherein the top surfaces of at least somecolumns (are generally convex.
 10. The method as claimed in claim 1,wherein the columns are configured so that when the masking material isremoved they form passageways aligned with the apertures and beingshaped for entrainment of droplets form the apertures.
 11. The method asclaimed in claim 1, wherein at least some of the columns have aconfiguration widening towards the substrate so that after removal ofthe masking material they form passageways which widen in a directionaway from the apertures.
 12. The method as claimed in claim 1, whereinat least some of the columns have a configuration widening towards thesubstrate so that after removal of the masking material they formpassageways which widen in a direction away from the apertures; andwherein the passageways are gradually tapered with a consistent slope.13. The method as claimed in claim 1, wherein the columns are configuredso that when the masking material is removed they form passagewaysaligned with the apertures and being shaped for entrainment of dropletsform the apertures; and wherein the passageways have a length in therange of range of 40 μm to 70 μm.
 14. An aperture plate comprising abody of metal configured with aerosol-forming apertures in a top surfaceand passageways aligned with and beneath the apertures, wherein themetal forms convex shapes around the apertures to provide afunnel-shaped entrance to the apertures.
 15. The aperture plate asclaimed in claim 14, wherein said passageways have a length in the rangeof 40 μm to 70 μm,
 16. The aperture plate as claimed in claim 14,wherein the passageways widen towards a lower side of the plate.
 17. Theaperture plate as claimed in claim 14, wherein the passageways have alength of 55 μm to 65 μm, and the aperture plate has a thickness in therange of 50 μm to 70 μm; and wherein the passageways have a width in therange of 20 μm to 40 μm.
 18. The aperture plate as claimed in claim 14,wherein the passageways have a length of 55 μm to 65 μm, and theaperture plate has a thickness in the range of 50 μm to 70 μm; andwherein the passageways have a width in the range of 20 μm to 40 μm; andwherein the passageways have a width in the range of 25 μm to 35 μm. 19.An aerosol-forming device comprising an aperture plate drive and anaperture plate support supporting an aperture plate comprising a body ofmetal configured with aerosol-forming apertures in a top surface andpassageways aligned with and beneath the apertures, wherein the metalforms convex shapes around the apertures to provide a funnel-shapedentrance to the apertures.